The Ets proteins, and other transcription factors which interact with Ets proteins, play a critical role in development of nearly every hematopoietic lineage, and are directly involved in the pathogenesis of many types of experimental and human leukemia. The overall goal of this program is to study specific members of this family in order to understand this essential role in normal hematopoiesis, and how abnormalities in structure and/or function of this class of proteins lead to leukemia. The future aims are to use this knowledge to design specific therapies for treatment of hematopoietic malignancies. The specific projects will include the following proposals: (1) C/EBP alpha signal transduction and myelopoiesis; (2) Function of ELF1 and a novel Ets factor NERF in beta cells; (3) Characterization of TEL, a new leukemogenic Ets protein; (4) The role of AML 1 in myeloid development and leukemia; (5) Structure and function of Ets/bZIP protein-DNA complexes; (6) MAP kinase regulation of TCF proteins. The administrative core shall be responsible for many interactive functions of the program, including regular studies of transcriptional regulation, protein-protein interactions, phosphorylation and signal transduction, knockout and knocking mice, and structure-function relationships, we will provide new information concerning a very interesting group of proteins whose functions and interactions are directly related to hematopoiesis and leukemogenesis.